Abstract:
Microglia play numerous important roles in brain development. From early embryonic stages through adolescence, these immune cells influence neuronal genesis and maturation, guide connectivity, and shape brain circuits. They also interact with other glial cells and structures, influencing the brain\'s supportive microenvironment. While this central role makes microglia essential, it means that early life perturbations to microglia can have widespread effects on brain development, potentially resulting in long-lasting behavioral impairments. Here, we will focus on the effects of early life psychosocial versus physiological stressors in rodent models. Psychosocial stress refers to perceived threats that lead to stress axes activation, including prenatal stress, or chronic postnatal stress, including maternal separation and resource scarcity. Physiological stress refers to physical threats, including maternal immune activation, postnatal infection, and traumatic brain injury. Differing sources of early life stress have varied impacts on microglia, and these effects are moderated by factors such as developmental age, brain region, and sex. Overall, these stressors appear to either 1) upregulate basal microglia numbers and activity throughout the lifespan, while possibly blunting their responsivity to subsequent stressors, or 2) shift the developmental curve of microglia, resulting in differential timing and function, impacting the critical periods they govern. Either could contribute to behavioral dysfunctions that occur after the resolution of early life stress. Exploring how different stressors impact microglia, as well as how multiple stressors interact to alter microglia\'s developmental functions, could deepen our understanding of how early life stress changes the brain\'s developmental trajectory. This article is part of the Special Issue on \"Microglia\".
摘要:
小胶质细胞在大脑发育过程中发挥着重要作用。从胚胎早期到青春期,这些免疫细胞影响神经元的发生和成熟,引导连接,塑造大脑回路。它们还与其他神经胶质细胞和结构相互作用,影响大脑的支持性微环境。虽然这种核心作用使得小胶质细胞必不可少,这意味着对小胶质细胞的早期生命扰动可以对大脑发育产生广泛的影响,可能导致持久的行为障碍。这里,我们将关注早期生活中的心理社会和生理应激源对啮齿动物模型的影响。心理社会压力是指导致压力轴激活的感知威胁,包括产前压力,或慢性产后压力,包括产妇分离和资源稀缺。生理应激是指身体上的威胁,包括母体免疫激活,产后感染,和创伤性脑损伤。生命早期应激的不同来源对小胶质细胞有不同的影响,这些影响受发育年龄等因素的调节,大脑区域,和性爱。总的来说,这些应激源似乎1)在整个生命周期中上调基底小胶质细胞的数量和活性,同时可能会削弱他们对随后压力的反应,或2)移动小胶质细胞的发育曲线,导致差分定时和功能,影响他们治理的关键时期。任何一种都可能导致早期生活压力解决后发生的行为功能障碍。探索不同的压力源如何影响小胶质细胞,以及多种压力源的经验如何相互作用以改变小胶质细胞的发育功能,可以加深我们对早期生活压力如何改变大脑发育轨迹的理解。